Over the past three decades, numerous different types of vascular prostheses have been produced for the replacement of arteries and veins. Reasonable success has been achieved with large caliber vascular prostheses (greater than 6 mm internal diameter) using man-made polymers, notably Dacron and Teflon in both knitted and woven configurations. Expanded polytetrafluoroethylene grafts have, to date, been the most successful of commercially available vascular prostheses in smaller caliber (4-6 mm) configurations, but it is fair to say that further improvements are necessary to produce a small caliber vascular prosthesis which can really challenge autologous saphenous vein for overall efficacy in both the peripheral vascular and coronary locations.
Biological vascular grafts represent the most effective alternative design pathway. With few exceptions, biological prostheses have been produced by methods which incorporated either proteolytic enzyme digestion followed by aldehyde fixation or aldehyde fixation alone. In some cases, further surface modifications were performed with a variety of chemicals to modify surface charge. The objectives were to stabilize tissues by crosslinking the proteinaceous components and to alter favorably the thrombogenic properties of the vessels. In all instances where aldehyde fixation was used the resultant vessel was altered considerably with respect to its mechanical properties. Fixation, however, appeared to render these vessels less antigenic. In the case of heart valves, previously fixed with aldehydes, further treatment with an anionic detergent, sodium dodecyl sulfate, substantially reduced the tendency of these devices to undergo calcification as disclosed in U.S. Pat. No. 4,323,358. Inhibition of calcification has also been attempted by incorporating a variety of inhibitors such as diphosphonates or chondroitan sulfates, as disclosed in U.S. Pat. Nos. 4,378,224 and 4,553,974. Both non-ionic and ionic detergents have been used in other ways, for example, to clear tissues of soluble materials prior to further treatment with aldehydes.
None of the treatments described above provided superior performance to that which would be achieved in blood vessel replacements, with artificial entirely man-made materials (eg. polytetrafluoroethylene). In contrast, biological valve replacements have an appreciably better record of performance than prostheses from synthetic materials. A new approach is based upon the realization that the extracellular matrix (which is produced by connective tissue cells, the major cell component of vessels) provides the vessel with inherent mechanical properties, forms a highly integrated and dense network of crosslinked fibers and is essentially resistant to extraction by detergents and physiological solutions.
The advantages of retaining intact this extracellular matrix, composed primarily of a collagenous component but also including elastin and other tightly bound substances, has been explored by Klaus, B. and Duhamel, R. (WO 84/0488)) for the production of sterile body implants. In their method, a variety of tissues were extracted sequentially with non-ionic and ionic detergents to yield structures essentially free of cellular membranes, nucleic acids, lipids and cytoplasmic components. Dependent upon the particular application, these structures were further modified by fixation and/or surface modification. In the case of canine carotid arteries, treated with their protocol, they achieved acceptable results after 90 days post-implantation.
Healthy arteries or veins should provide material most suitable for the replacement of damaged vessels in terms of biological and mechanical properties.
An extraction protocol has been developed which provides substantially improved biological protheses which are highly biocompatible and long lasting replacements. The biological prosthesis is equivalent in compliance and mechanical strength to a healthy vessel through retention of elastic properties and highly resistant to calcification and thrombogenesis and hence in most situations, avoids the need to administer anti-thrombosis drugs.
Accordingly, the invention removes soluble small and high molecular weight substances from natural tissue which will be used as the prosthesis while retaining the insoluble, collagenous and elastic "backbone" of the natural tissue. The tissue is extracted by a series of detergent and non-proteolytic enzymatic treatments.